Axicabtagene ciloleucel compared to tisagenlecleucel for the treatment of aggressive B-cell lymphoma.

Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are CD19-targeted chimeric antigen receptor (CAR) T cells approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). We performed a retrospective study to evaluate safety and efficacy of axi-cel and tisa-cel outside the setting of a clinical trial. Data from consecutive patients with R/R LBCL who underwent apheresis for axi-cel or tisa-cel were retrospectively collected from 12 Spanish centers. A total of 307 patients underwent apheresis for axi-cel (n=152) and tisa-cel (n=155) from November 2018 to August 2021, of which 261 (85%) received a CAR T infusion (88% and 82%, respectively). Median time from apheresis to infusion was 41 days for axi-cel and 52 days for tisa-cel (P=0.006). None of the baseline characteristics were significantly different between both cohorts. Both cytokine release syndrome and neurologic events (NE) were more frequent in the axi-cel group (88% vs. 73%, P=0.003, and 42% vs. 16%, P<0.001, respectively). Infections in the first 6 months post-infusion were also more common in patients treated with axi-cel (38% vs. 25%, P=0.033). Non-relapse mortality was not significantly different between the axi-cel and tisa-cel groups (7% and 4%, respectively, P=0.298). With a median follow-up of 9.2 months, median PFS and OS were 5.9 and 3 months, and 13.9 and 11.2 months for axi-cel and tisa-cel, respectively. The 12-month PFS and OS for axi-cel and tisa-cel were 41% and 33% (P=0.195), 51% and 47% (P=0.191), respectively. Factors associated with lower OS in the multivariate analysis were increased lactate dehydrogenase, ECOG ≥2 and progressive disease before lymphodepletion. Safety and efficacy results in our real-world experience were comparable with those reported in the pivotal trials. Patients treated with axi-cel experienced more toxicity but similar non-relapse mortality compared with those receiving tisa-cel. Efficacy was not significantly different between both products.

Relevance of renin expression by real-time PCR in acute myeloid leukemia.

The search for useful molecular markers in the diagnosis of AML and in the follow-up of minimal residual disease (MRD) has been the focus of many recent studies. Previous research showed that, while normal bone marrow cells lack expression of renin, myeloid blasts have been reported to do so. The aim was to study the expression of the renin gene by the use of real-time quantitative PCR (RQ-PCR) at diagnosis in acute myeloid leukemia patients (AML) and to assess its possible relevance in the prognosis and outcome of such patients. This study analysed 76 samples from patients with AML, with follow-up of positive patients. Thirty-one patients (41%) were positive for renin gene expression at diagnosis. All renin-positive patients at diagnosis showed no expression during complete remission (CR), but expression recurred in those experiencing relapse and persisted when the disease was refractory to treatment. Although the results suggest that the sub-group of renin-positive AML patients might have a worse outcome and a higher relapse rate (at 5 years, the projected rate of disease-free survival was 18.5 +/- 9.8% for renin-positive and 23.5 +/- 8.8% for renin-negative patients), no significant differences were found. It is believed that further studies should aim to validate whether such a difference exists, using a much larger and homogeneus group of patients.